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Abstract：Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.Keywords：Robotic surgical system;Prostate cancer (PCa);Robot-assisted radical prostatectomy (RARP);Intelligent medicine58|14|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13
PERSPECTIVE
Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021 AI Introduction
Abstract：Background:Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021.Methods:Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and socio-demographic index (SDI) was also analyzed.Results:In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: –1.52; 95% uncertainty interval (UI) –1.66 to –1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000–16.39/100,000) in 2021, with an EPAC for ASIR <0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03–11.95) and 285.62 (95% UI 209.42–379.65). The burden associated with SAH primarily affected individuals aged between 50–69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework.Conclusions:The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.Keywords：Subarachnoid hemorrhage (SAH);Global Burden of Disease Study (GBD) 2021;Incidence;Mortality;Disability-adjusted life-years (DALYs)74|52|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13
Abstract：Background:Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.Methods:Sensitivity analysis was based on a randomized, two-arm, multicenter, double-blind, controlled trial. The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs outputs in 100 consecutive cases (from August to September 2013 from Emilia Romagna region, Italy). Patients included an agent-based TCS10 group (10 mg, single intravenous bolus before surgery; n=56) and control group (n=44) and the association with cytokines, lactate, and bleeding-blood transfusion episodes with the prior-risk log odds for mortality rate in time-to-event was analyzed.Results:Thirty-day mortality was significantly improved in the TCS10 group vs. control group (0 vs. 8 deaths, P<0.0001). Baseline levels of interleukin (IL)-6, IL-10, and lactate were associated with bleeding episodes, independent of TCS10 treatment [odds ratio (OR)=1.90, 95% confidence interval (CI) 1.39–2.79; OR=1.53, 95% CI 1.17–2.12; and OR=2.92, 95% CI 1.40–6.66, respectively], while baseline level of Fms-like tyrosine kinase 3 ligand (Flt3L) was associated with lower bleeding rates in TCS10-treated patients (OR=0.31, 95% CI 0.11–0.90, P=0.03). For every 8 TCS10-treated patients, 1 bleeding case was avoided. Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group (OR=0.32, 95% CI 0.14–0.73, P=0.01). For every 4 TCS10-treated patients, 1 transfusion case was avoided.Conclusions:Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care. To introduce the technology readiness level in real-life critically ill patients, further large-scale studies are required.Keywords：Critical care;Melanocortin;cytokine;Mortality;Survival;Bleeding;Transfusion51|28|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13![FDA-approved cannabidiol [Epidiolex<sup>®</sup>] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis](https://founder-rc-product.oss-cn-zhangjiakou.aliyuncs.com/drawImage/202510/16/19/75339493/03978694-8f3a-46fb-8756-ec352b3c8392_m.jpg?response-content-type=image%2Fjpeg)
Abstract：Background:Chronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex®, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI.Methods:Six months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks. Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory, object location memory, pattern separation, and sucrose preference. The effect of CBD on hyperalgesia was also examined. The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.Results:GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia, whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia. Additionally, CBD treatment alleviated hyperalgesia in GWI rats. Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling. Furthermore, there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis. In contrast, the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling, normalized concentrations of proinflammatory cytokines and oxidative stress markers, and improved neurogenesis. Notably, CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.Conclusions:The use of an FDA-approved CBD (Epidiolex®) has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI. Importantly, the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.Keywords：Gulf War Illness (GWI);Anhedonia;Activated microglia;Cannabidiol (CBD);Chronic neuroinflammation;Cognition;Hippocampal neurogenesis;Inflammasomes;Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling;Memory dysfunction;NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes;Oxidative stress43|27|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13Effectiveness of chest pain center accreditation on the hospital outcome of acute aortic dissection: a nationwide study in China AI Introduction
Abstract：Background:The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD).Methods:We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surgery. Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions.Results:The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P<0.001 and 2.9% vs. 5.4%, P<0.001, respectively) as well as a notably higher rate of Stanford type A AAD surgery (61.1% vs. 42.1%, P<0.001) compared with the pre-accreditation group. After adjusting for potential covariates, CPC accreditation was associated with substantially reduced risks of in-hospital mortality (adjusted OR=0.644, 95% CI 0.599–0.693) and misdiagnosis (adjusted OR=0.554, 95% CI 0.493–0.624), along with an increase in the proportion of patients undergoing Stanford type A AAD surgery (adjusted OR=1.973, 95% CI 1.797–2.165). Following CPC accreditation, there were significant reductions in in-hospital mortality across various regions, particularly in Western regions (from 21.5% to 14.1%). Moreover, CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities (adjusted OR: 0.607 vs. 0.713).Conclusion:CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD.Keywords：Acute aortic dissection (AAD);Chest pain center (CPC);Accreditation;In-hospital outcomes61|22|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13
Abstract：Background:With advancements in burn treatment and intensive care leading to decreased mortality rates, a growing cohort of burn survivors is emerging. These individuals may be susceptible to frailty, characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging, which significantly complicates their recovery process. To date, no study has investigated burns as a potential risk factor for frailty. This study aimed to determine the short-term prevalence of frailty among burn survivors’ months after injury and compare it with that of the general population.Methods:A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury (RE-ENERGIZE) trial, an international randomized-controlled trial involving 1200 burn injury patients with partial- or full-thickness burns. Participants who did not complete the 36-Item Short Form Health Survey (SF-36) questionnaire were excluded. Data for the general population were obtained from the 2022 National Health Interview Survey (NHIS). Frailty was assessed using the FRAIL (Fatigue, Resistance, Ambulation, Illness, Loss of weight) scale. Due to lack of data on loss of weight, for the purposes of this study, malnutrition was used as the fifth variable. Illness and malnutrition were based on admission data, while fatigue, resistance, and ambulation were determined from post-discharge responses to the SF-36. The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status. Within the burn group, patients were divided into different subgroups based on their frailty status, and the differences in their (instrumental) activities of daily living (iADL and ADL) were compared. A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.Results:Out of the 1200 burn patients involved in the study, 600 completed the required questionnaires [follow-up time: (5.5±2.3) months] and were matched to 1200 adults from the general population in the U.S. In comparison to the general population, burn patients exhibited a significantly higher likelihood of being pre-frail (42.3% vs. 19.8%, P<0.0001), or frail (13.0% vs. 1.0%, P<0.0001). When focusing on specific components, burn patients were more prone to experiencing fatigue (25.8% vs. 13.5%, P<0.0001), limited resistance (34.0% vs. 2.7%, P<0.0001), and restricted ambulation (41.8% vs. 3.8%, P<0.0001). Conversely, the incidence rate of illness was observed to be higher in the general population (1.2% vs. 2.8%, P=0.03), while no significant difference was detected regarding malnutrition (2.3% vs. 2.6%, P=0.75). Furthermore, in comparison with robust burn patients, it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL. The frail cohort reported the most pronounced limitation.Conclusions:Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury. Burn survivors experience compromised fatigue, resistance, and ambulation, while rates of illness and malnutrition were lower or unchanged, respectively. These results underscore the critical need for early identification of frailty after a burn injury, with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists, community physicians, physiotherapists, nutritionists, and social workers. This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.Keywords：Burn injury;Quality of life;Frailty;aging;Activities of daily living44|29|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13
RESEARCH
Advances in the mechanism of small nucleolar RNA and its role in DNA damage response AI Introduction
Abstract：Small nucleolar RNAs (snoRNAs) were previously regarded as a class of functionally conserved housekeeping genes, primarily involved in the regulation of ribosome biogenesis by ribosomal RNA (rRNA) modification. However, some of them are involved in several biological processes via complex molecular mechanisms. DNA damage response (DDR) is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases. It has recently been revealed that snoRNAs are involved in DDR at multiple levels, indicating their relevant theoretical and clinical significance in this field. The present review systematically addresses four main points, including the biosynthesis and classification of snoRNAs, the mechanisms through which snoRNAs regulate target molecules, snoRNAs in the process of DDR, and the significance of snoRNA in disease diagnosis and treatment. It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.Keywords：Small nucleolar RNAs (snoRNAs);DNA damage response (DDR);Oxidative stress;Cell cycle checkpoints;DNA damage repair;Cell death50|22|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13Targeting mitochondrial quality control: new therapeutic strategies for major diseases AI Introduction
Abstract：Mitochondria play a crucial role in maintaining the normal physiological state of cells. Hence, ensuring mitochondrial quality control is imperative for the prevention and treatment of numerous diseases. Previous reviews on this topic have however been inconsistencies and lack of systematic organization. Therefore, this review aims to provide a comprehensive and systematic overview of mitochondrial quality control and explore the possibility of targeting the same for the treatment of major diseases. This review systematically summarizes three fundamental characteristics of mitochondrial quality control, including mitochondrial morphology and dynamics, function and metabolism, and protein expression and regulation. It also extensively examines how imbalances in mitochondrial quality are linked to major diseases, such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. Additionally, the review explores innovative approaches to target mitochondrial quality control, including using small molecule drugs that regulate critical steps in maintaining mitochondrial quality, nanomolecular materials designed for precise targeting of mitochondria, and novel cellular therapies, such as vesicle therapy and mitochondrial transplantation. This review offers a novel perspective on comprehending the shared mechanisms underlying the occurrence and progression of major diseases and provides theoretical support and practical guidance for the clinical implementation of innovative therapeutic strategies that target mitochondrial quality control for treating major diseases.Keywords：Major diseases;Mitochondrial quality control;Mitochondrial targeted therapy81|33|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13
REVIEW
Keywords：Parkinson’s disease;Gut microbiota;Functional magnetic resonance imaging54|31|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13The Frank-Starling mechanism is not enough: blood volume expansion prominently decreases pulmonary O2 uptake AI Introduction
Keywords：Blood volume expansion;Placebo-controlled;Cross-over;Pulmonary O2 uptake;Cardiac performance;Aerobic exercise capacity;Cardiorespiratory fitness31|17|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13Enhancing adherence for total body skin examination in post-surgical veterans: an interventional study at an urban Veterans Affairs center AI Introduction
Keywords：Skin cancer screening;Quality improvement;Total body skin check;Veteran population43|11|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13A prediction model for moderate to severe acute kidney injury in people with heart failure AI Introduction
Keywords：Acute kidney injury (AKI);heart failure;Prediction model;Machine learning49|45|0<HTML><L-PDF> <Meta-XML>Updated：2025-12-13
LETTER TO THE EDITOR
